The National Institute on Alcohol Abuse and Alcoholism (NIAAA) seeks to expand research applying genetic epidemiologic methods to studies of substance and alcohol use disorders (SUDs/AUDs, drug or alcohol abuse and dependence). Previous studies using twin, adoption, and family approaches indicate that genetic factors substantially contribute to the vulnerability to SUDs/AUDs. Shared environmental factors have also been shown strongly to influence risk, while heritability estimates generally rise with age and with progression from substance use to disorder. Significant advances have been made in our understanding of the onset and progression of SUDs/ A UDs and in defining a disinhibited phenotype. Building on these findings, new studies are needed to apply genetic epidemiology approaches to advance our understanding in a variety of areas, integrate as well as differentiate genetic and environmental factors in the onset and maintenance of SUDs/AUDs, broaden and refine phenotypic definitions of SUDs/AUDs, guide the translation of etiologic findings to treatment, prevention, gene-finding, and meet the methodologic challenges of the field. A variety of research approaches have established that SUDs/AUDs are heritable complex disorders, and that family history of SUD/ AUD is probably the most potent risk factor for these disorders. Heritability estimates have been high, and shared environmental effects appear to be strong. Genetic epidemiologic studies have highlighted the nature of SUDs/ A UDs as a developmental disorder, particularly as part of a general vulnerability to problem behavior associated with disinhibition. A surprising degree of non-specificity has been found in regard to choice of substance and gender; that is, many risk factors appear to operate similarly in the vulnerability to abuse and dependence for a variety of drugs in men and women. Increasingly sophisticated approaches have also been applied to understand the high prevalence of psychiatric comorbidity with SUDs/AUDs. Important findings are emerging on the roles of gene-environment correlation and gene-environment interaction in elucidating the development of substance and alcohol use and SUDs/ AUDs.